The objective of this project is to study the regulation of branching morphogenesis of the lung. In Aim 1, the spatial and temporal localization of transcripts and translated proteins for CRBP1, CRABP1, RARa, RARb, and RARg will be examined by the techniques of whole mount in situ hybridization and immunohistochemistry. In Aim 2, an in vitro rat lung explant system and in vivo animal model will be used to examine the regulation of RAR and RXR mRNAs and proteins by all-trans RA and 9-cis RA. In Aim 3, the effect of disruption of endogenous RA signaling on the pattern of branching, as well as on the expression of mediators of retinoid function, will be determined in the developing lung in vitro. In Aim 4, the effect of disruption of retinoid signaling on the expression of genes encoding secondary signaling proteins such as sonic hedgehog (shh) also will be determined in vitro. Changes in the expression and localization of these transcripts will be correlated with changes in gross morphology and histologic differentiation of the lung.